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Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.

Woo HD, Chiu WA, Jo S, Kim J - PLoS ONE (2015)

Bottom Line: Low doses of cadmium can cause adverse health effects.Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level.The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang-si, Korea.

ABSTRACT

Background: Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ.

Objectives: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs.

Methods: A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction.

Results: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group.

Conclusion: The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of the study selection process.
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pone.0126680.g001: Flow diagram of the study selection process.

Mentions: A total of 27 studies were identified and 14 studies were excluded due to the following reasons: 3 studies did not include BMD; 2 studies did not include human population; 2 studies did not include renal damage markers; 3 studies included BMD for lifetime cadmium intake or cadmium concentration in rice; 3 studies did not include cut-off points or calculation method for BMD; and 1 study was a review article. Thirteen studies were finally selected for the review of the BMD derived from cadmium-induced renal damage (Fig 1) [16–19,22–30]. The most studied renal tubular damage markers were β2-MG and NAG for the urinary cadmium BMD. The BMD calculated from occupationally exposed population were included only in subgroup analysis. Nine studies (21 data points) for β2-MG and 8 studies (16 data points) for NAG were used for the pooled BMD estimates with exception of studies used occupationally exposed population. Selected studies reporting the BMD for the induction of β2-MG and NAG by cadmium were reported (Tables 1 and 2).


Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.

Woo HD, Chiu WA, Jo S, Kim J - PLoS ONE (2015)

Flow diagram of the study selection process.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430293&req=5

pone.0126680.g001: Flow diagram of the study selection process.
Mentions: A total of 27 studies were identified and 14 studies were excluded due to the following reasons: 3 studies did not include BMD; 2 studies did not include human population; 2 studies did not include renal damage markers; 3 studies included BMD for lifetime cadmium intake or cadmium concentration in rice; 3 studies did not include cut-off points or calculation method for BMD; and 1 study was a review article. Thirteen studies were finally selected for the review of the BMD derived from cadmium-induced renal damage (Fig 1) [16–19,22–30]. The most studied renal tubular damage markers were β2-MG and NAG for the urinary cadmium BMD. The BMD calculated from occupationally exposed population were included only in subgroup analysis. Nine studies (21 data points) for β2-MG and 8 studies (16 data points) for NAG were used for the pooled BMD estimates with exception of studies used occupationally exposed population. Selected studies reporting the BMD for the induction of β2-MG and NAG by cadmium were reported (Tables 1 and 2).

Bottom Line: Low doses of cadmium can cause adverse health effects.Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level.The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang-si, Korea.

ABSTRACT

Background: Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ.

Objectives: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs.

Methods: A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction.

Results: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group.

Conclusion: The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

No MeSH data available.


Related in: MedlinePlus